The principal objective of this research is to evaluate the relative significance of elastolytic activity in the pathogenesis of emphysema associated with cigarette smoking. Since the elastases produced by leukocytes and by alveolar macrophages are known to differ in properties this proposal will entail or study the relative contribution of leukocyte and alveolar macrophage elastase activities to the total elastolytic activity on lung tissue of animals exposed to cigarette smoke. Rats will be exposed to cadmium aerosols and cigarette smoke, and a time study will be made of the lung lavage fluid with respect to the relative number of leukocytes and macrophage, elastase activity in the presence and absence of various inhibitors known to be specific for one or the other of the elastases, and concomitant pathological changes in the lung tissue. This animal model system will also be used to test the therapeutic effectiveness of human albumin microspheres to which have been attached specific inhibitors of leukocyte elastase or macrophage elastase.